Prescription Opioid Dependence Physiology Emotion and Treatment Outcome

描述（由申请人提供）：临床医生长期以来一直意识到阿片类药物依赖治疗的前三个月复发率高，以及它与阿片类药物戒断后持续但定义松散的失调状态的理论关系。“不平衡”一词已被应用于与阿片类药物依赖相关的下丘脑轴和大脑奖励系统的变化，这些变化可能在解毒后持续存在。下丘脑轴的正常内稳态受到干扰，对自然奖励（如食物、性等）的反应受到抑制，对药物相关刺激的反应明显增强，患者抱怨情绪消极（快感缺乏）。在动物模型和患者中，解毒后各种失调因素的持续时间是不确定的；在啮齿动物身上的发现如何以及是否可以转化为有临床意义的数据也是一个问题。重要的是，目前尚不清楚这些数据是否具有预后意义；特别是，它们是否与依赖处方阿片类药物的患者有关。拟议的研究将对最近解毒的处方阿片类药物依赖的男性和女性患者进行为期一个月的住院药物康复治疗，在Caron基金会（Wernersville， PA）另外3个月的延长住宿护理，以及出院后1个月和3个月的随访。最近的经验表明，每个月有5名患者符合入组条件。那些可能从30天计划过渡到延长护理的患者通常在30天计划的第10天确定。这些患者中有5%在历史上未能完成延长护理计划。这项初步研究的结果包括：1)评估额叶皮质和心理生理对药物提示和自然奖励的反应；2)日皮质醇；3)对7名新近解毒的处方阿片类药物依赖患者（DPO）、7名在无药物监护下居住超过90天的DPO患者和7名正常对照组（Ps）进行8天的客观和主观睡眠测量，以及自我报告的情绪、压力和渴望。两组之间在这些指标上的统计学显著差异支持了对这些变量进行长期纵向研究的必要性。该研究的总体目标是比较最近解毒依赖处方阿片类药物的患者与正常对照p的基线中枢神经系统反应、每日皮质醇、睡眠和每日及日内情绪、压力和渴望的变异性；并且，在一段时间内监测患者的这些措施，从排毒后的10天到最长的监督无药居住期。用于分析密集测量过程的新统计方法将用于增进对这些测量之间的时间关系的理解，以及它们与出院后1个月和3个月的药物使用状况的可能预测关系。拟议研究的结果将有助于推进处方阿片类药物依赖的循证治疗指南，以及成瘾性疾病的转化研究。

DESCRIPTION (provided by applicant): Clinicians have long been aware of the high rate of relapse in the first three months of treatment for opiate dependence and its theoretical relationship to a persistent, but loosely defined, dysregulated state consequent to opiate withdrawal. The term allostasis has been applied to the changes in the HPA axis and the brain reward system associated with opiate dependence that may persist following detoxification. The normal homeostasis of the HPA axis is disturbed, responses to natural rewards (e.g., food, sex, etc.) are dampened, the response to drug-related stimuli is markedly enhanced, and patients complain of negative mood (anhedonia). The duration of various elements of dysregulation after detoxification, in animal models and in patients, is uncertain; as is the question of how & whether findings in the rodent can be translated into clinically meaningful data. Importantly, it i unclear if these data have prognostic significance; and, in particular, whether they are relevant to patients dependent on prescription opioids. The proposed study will follow a population of recently detoxified male and female patients with prescription opioid dependence through a one month period of inpatient drug rehabilitation treatment, 3 additional months of extended residential care at the Caron Foundation (Wernersville, PA), and 1 and 3 months post-discharge. Recent experience indicates that 5 patients/month would be eligible for enrollment in the study. Those patients likely to transition from the 30-day program to extended care are typically identified by the 10th day of the 30 day program. 5% of these patients have historically failed to complete the extended care program. The proposed study follows upon the results of a pilot study that included: 1) assessments of frontal cortical and psychophysiological responses to slide sets of drug cues and natural rewards; 2) diurnal cortisol; and, 3) 8 days of objective an subjective measures of sleep, as well as self-reported mood, stress and craving in 7 recently detoxified patients dependent on prescription opioids (DPO), 7 DPO patients who had been in supervised drug-free residential care for 90+ days, and 7 normal control participants (Ps). The statistically significant differences between the groups on these measures support the need for a longitudinal study of these variables in patients over time. The overall objective of the study will be to compare the baseline CNS responses, diurnal cortisol, sleep & daily and within- day variability of mood, stress and craving of recently detoxified patients dependent upon prescription opioids, with normal control Ps; and, to monitor these measures in the patients over time, from ten days post detox through the maximum period of supervised drug-free residence. New statistical methods for the analysis of intensively-measured processes will be used to advance understanding of the temporal relationships between these measures, and their possible predictive relationship to drug-using status one and three months after discharge. The findings from the proposed research will help to advance evidence-based, treatment guidelines on prescription opioid dependence, as well as translational research on addictive disorders.